Increased Activity of a Renal Salt Transporter (ENaC) in Diabetic Kidney Disease

Hypertension Clinical Trial

Official title:

Increased Activity of the Epithelial Sodium Channel (ENaC) in Diabetic Nephropathy

Clinical Trial Details — Status: Unknown status

Administrative data

• NCT number: NCT01918488
• Other study ID #: 2013-052
• Secondary ID: 13-04-R94-A4513-
• Status: Unknown status
• Phase: N/A
• First received: July 31, 2013
• Last updated: October 14, 2013
• Start date: October 2013

Study information

• Verified date: October 2013
• Source: University of Southern Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of the study is to determine whether a diuretic drug called amiloride is capable of increasing renal salt excretion and thereby decrease blood pressure in diabetic patients with kidney disease. Our hypothesis states that amiloride is capable of reducing blood pressure in these patients and thus decrease the cardiovascular risk associated with diabetic kidney disease.

Recruitment information / eligibility

• Status: Unknown status
• Enrollment: 80
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

Inclusion Criteria:

• Type 1 diabetes

• Negative pregnancy test at inclusion and taking contraceptive medication

• One group with diabetic nephropathy and overt proteinuria

• One normoalbuminuric group without nephropathy

• Creatinine clearance > 40 ml/min

Exclusion Criteria:

• Type 2 diabetes

• Receiving amiloride, glucocorticoids, aldosterone or spironolactone

• Clinically relevant organic or systemic disease including malignancy

Related Conditions & MeSH terms

• Diabetic Nephropathies
• Hypertension
• Kidney Diseases

Intervention

Dietary Supplement:
• Standardized salt diet
200 mmol NaCl per day given as three meals daily for 4 consecutive days.

Drug:
• Amiloride
Amiloride tablet 20 mg two times daily (morning and afternoon) for two consecutive days.

Locations

Country	Name	City	State
Denmark	Cardiovascular and Renal Research	Odense

Sponsors (5)

Lead Sponsor	Collaborator
University of Southern Denmark	Danish Heart Foundation, Odense University Hospital, Region of Southern Denmark, The Ministry of Science, Technology and Innovation, Denmark

Country where clinical trial is conducted

Denmark, 

References & Publications (4)

Buhl KB, Friis UG, Svenningsen P, Gulaveerasingam A, Ovesen P, Frederiksen-Møller B, Jespersen B, Bistrup C, Jensen BL. Urinary plasmin activates collecting duct ENaC current in preeclampsia. Hypertension. 2012 Nov;60(5):1346-51. doi: 10.1161/HYPERTENSIONAHA.112.198879. Epub 2012 Sep 17. — View Citation

Saha C, Eckert GJ, Ambrosius WT, Chun TY, Wagner MA, Zhao Q, Pratt JH. Improvement in blood pressure with inhibition of the epithelial sodium channel in blacks with hypertension. Hypertension. 2005 Sep;46(3):481-7. Epub 2005 Aug 22. Review. — View Citation

Svenningsen P, Bistrup C, Friis UG, Bertog M, Haerteis S, Krueger B, Stubbe J, Jensen ON, Thiesson HC, Uhrenholt TR, Jespersen B, Jensen BL, Korbmacher C, Skøtt O. Plasmin in nephrotic urine activates the epithelial sodium channel. J Am Soc Nephrol. 2009 Feb;20(2):299-310. doi: 10.1681/ASN.2008040364. Epub 2008 Dec 10. — View Citation

Svenningsen P, Uhrenholt TR, Palarasah Y, Skjødt K, Jensen BL, Skøtt O. Prostasin-dependent activation of epithelial Na+ channels by low plasmin concentrations. Am J Physiol Regul Integr Comp Physiol. 2009 Dec;297(6):R1733-41. doi: 10.1152/ajpregu.00321.2009. Epub 2009 Sep 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	24-hour urinary sodium excretion induced by amiloride		Change from baseline urinary sodium excretion at 24 hours after amiloride administration
Secondary	Office blood pressure measurements		Change from baseline office blood pressure at day 4 of salt diet and at 24 hours after amiloride administration